Effects of extremely preterm birth on cytokine and chemokine responses induced by T-cell activation during infancy

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology Pub Date : 2024-05-10 DOI:10.1002/cti2.1510

Dhanapal Govindaraj, Georg Bach Jensen, Khaleda Rahman Qazi, Eva Sverremark-Ekström, Thomas Abrahamsson, Maria C Jenmalm

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Abstract

Objectives

Extremely preterm (EPT; gestational week < 28 + 0, < 1000 g) neonates are vulnerable to infections and necrotising enterocolitis, important contributors to mortality and morbidity. However, knowledge regarding their immune maturation remains limited. We here investigated the longitudinal development of functional T-cell capacity in EPT infants.

Methods

Peripheral blood mononuclear cells were isolated at 14th and 28th day (D) and at gestational week 36 + 0 (Gw36) from EPT infants, participated in a randomised, double-blind, placebo-controlled study of Lactobacillus reuteri DSM 17938 probiotic supplementation. Blood collected from 25 full-term (FT) infants at D14 was used as control. The secretion of immune mediators was determined through comprehensive Luminex panels after stimulation with human T-cell activator CD3/CD28 beads.

Results

The levels of many mediators were low in EPT infants at D14, whereas the secretion of several chemokines was higher in EPT than in FT infants. Furthermore, Th2:Th1 cytokine ratios were higher in EPT than in FT infants. Progressively elevated secretion of, for example, IFN-γ, TNF and IL-17A in EPT infants was observed from D14 to D28 and then at Gw36. Elevated levels were observed for many proinflammatory mediators at D28. Probiotic supplementation or perinatal factors (e.g. clinical chorioamnionitis, preeclampsia and delivery mode) did not influence the cytokine and chemokine responses.

Conclusions

Immune mediators induced by T-cell activation in EPT infants were mainly reduced at D14 and Th2 skewed compared to those in FT infants, but mostly recovered at Gw36, indicating immune maturation. Increased proinflammatory responses at D28 may be related to the heightened risk of severe immune-associated complications seen in EPT infants.

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极早产对婴儿期 T 细胞激活诱导的细胞因子和趋化因子反应的影响

目的极早产（EPT；孕周 28 + 0，体重 1000 克）新生儿很容易受到感染和坏死性小肠结肠炎的侵袭，这是导致死亡和发病的重要因素。然而，有关他们免疫成熟的知识仍然有限。我们在此研究了 EPT 婴儿 T 细胞功能的纵向发展。方法在 EPT 婴儿出生后第 14 天和第 28 天（D）以及妊娠 36+0 周（Gw36）分离出外周血单核细胞，这些婴儿参加了一项关于补充 Lactobacillus reuteri DSM 17938 益生菌的随机、双盲、安慰剂对照研究。25 名足月（FT）婴儿在出生后 14 天采集的血液作为对照。在使用人 T 细胞激活剂 CD3/CD28 微珠刺激后，通过 Luminex 综合检测板测定免疫介质的分泌情况。结果 EPT 婴儿在 14 岁时许多介质的水平较低，而几种趋化因子在 EPT 婴儿中的分泌高于 FT 婴儿。此外，EPT 婴儿的 Th2:Th1 细胞因子比率高于 FT 婴儿。EPT婴儿的IFN-γ、TNF和IL-17A等细胞因子的分泌量从D14到D28，然后到Gw36逐渐升高。D28时，许多促炎介质水平升高。益生菌补充剂或围产期因素（如临床绒毛膜羊膜炎、先兆子痫和分娩方式）并不影响细胞因子和趋化因子的反应。结论与FT婴儿相比，EPT婴儿T细胞活化诱导的免疫介质主要在D14时减少，并偏向Th2，但在Gw36时大部分恢复，表明免疫成熟。EPT婴儿出现严重免疫相关并发症的风险增加可能与D28时促炎反应增加有关。

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来源期刊

Clinical & Translational Immunology Medicine-Immunology and Allergy

CiteScore

12.00

自引率

1.70%

发文量

审稿时长

13 weeks

期刊介绍： Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.